System for treating a sebaceous gland

ABSTRACT

One aspect of the invention provides a system of treating a sebaceous gland in human skin with light energy to reduce acne symptoms. The system includes: a composition comprising a metallic nanoparticle dispersed within a carrier; means to vibrate at least a portion of the skin surface to which the composition is applied; means to selectively remove at least some of the composition from the skin surface after application of the means to vibrate, while leaving the metallic nanoparticles in proximity to or within the sebaceous gland; and means to optically irradiate the skin to which the composition was applied with light energy after removal of at least some of the composition from the skin surface.

CROSS REFERENCE TO RELATED APPLICATIONS

The application is a continuation of U.S. patent application Ser. No.14/627,470, filed Feb. 20, 2015, which application is a continuation ofU.S. patent application Ser. No. 12/787,655, filed May 26, 2010, nowissued as U.S. Pat. No. 8,961,450, which application claims the benefitof U.S. Provisional Patent Application Ser. No. 61/181,228, filed May26, 2009. The disclosures of each of the foregoing patent applicationsare incorporated herein in their entireties by reference.

FIELD OF THE INVENTION

The present invention is directed to a method and apparatus fordelivering a substance, e.g., a therapeutic substance, to sebaceousglands and/or hair follicles.

BACKGROUND INFORMATION

FIG. 1 shows a hair follicle structure 100, which includes a hairfollicle 110, hair shaft 120 and one or more associated sebaceous glands130. A small gap 125 is generally present between the hair shaft 120 andthe sides of the follicle 110 in the upper portion of the folliclestructure 100 leading to the skin surface 115. One or more sebaceousglands 130 are often connected to this gap via a duct 135, as shown inFIG. 1.

Sebaceous glands 130 secrete an oily substance called sebum 140, whichis a mixture of lipids and debris from dead cells shed by the gland 130.The sebum 140 is deposited into the upper portion (infundibulum) of thehair follicle 110, and eventually may rise up to the skin surface 115.Sebum 140 can lubricate and protect hair shafts 120, act as amoisturizer, and can also help to seal the follicle opening 125 fromexternal substances.

Sebum accumulation and/or blockage of the duct 135 between the sebaceousgland 130 and the hair follicle 110 by sebum 140 can be a major cause ofthe common skin condition acne vulgaris (generally referred to as‘acne’). Sebum blockages can enlarge to form blackheads or whiteheads.Redness, swelling, and infection may also occur. These acne symptoms canbe aesthetically undesirable and socially stigmatizing, and they canalso lead to the formation of disfiguring scars.

Present approaches for alleviating acne symptoms and avoiding moreserious complications include application of topical solutions ofsubstances such as benzoyl peroxide (available over-the-counter or byprescription) or salicylic acid, or prescription antibiotics such aserythromycin, clindamycin, or tetracycline derivatives. Topicalretinoids can also be applied to alleviate acne symptoms. Retinoidsinclude tretinoin (brand name Retin-A), adapalene, and tazarotene andthe non-prescription retinol or derivatives. Retinoids appear toinfluence cells in the follicle lining, which can help to preventhyperkeratinization of these cells that can lead to blockages.

The effectiveness of such topical treatments, particularly solutionscontaining retinoids, may generally be limited by the ability of thetopical solutions to penetrate deeply into the follicle 110 and into thesebaceous gland 130 itself. Accumulation of sebum 140 and debris in thehair follicle 110 and/or duct 135 leading into the sebaceous gland 130can inhibit penetration of topical solutions into the follicle regionwhere they may be more efficacious.

Oral intake of isotretinoin, a retinoid (available under the brand namesACCUTANE®, SOTRET®, CLARUS™, etc.) has been shown to provide long-termreduction of acne symptoms or severity thereof. Isotretinoin can be veryeffective for treating severe cases of acne. However, oraladministration of isotretinoin is believed to cause significant sideeffects, including liver damage and birth defects when used by pregnantwomen. For these reasons, treatment of acne using oral administration ofisotretinoin generally requires close monitoring and a specifiedtimetable for treatment cycles.

Other techniques that can be used to treat acne with varying degrees ofeffectiveness include phototherapy (e.g., photodynamic therapy (“PDT”)or treatment with various lasers or intense pulsed light sources). PDTgenerally involves topical application of a solution containing5-aminolevulinic acid (ALA) or other photosensitizer precurosors orphotosensitizers, followed by irradiation with optical energy toactivate the photosensitizer and selectively affect certain tissueswhere the photosensitizer is present. PDT techniques for treating acneare described, e.g., in U.S. Pat. No. 6,897,238, and various substancesthat may be used as photosensitizers in PDT procedures are described,e.g., in U.S. Pat. No. 6,034,267.

Follicular keratosis is a common condition that is characterized byexcess production of keratin that can block follicles, and producesymptoms such as rashes, swelling, pain and/or ingrown hairs. Althoughthere is no known cure for follicular keratosis, symptoms can berelieved through application of substances such as topical solutions ofvitamin A or benzoyl peroxide.

Topical solutions, lotions, etc. are also marketed for application tothe scalp to stimulate hair growth, reduce a rate of hair loss, etc.These solutions can contain substances such as minoxidil, azealic acid,and/or dyhydrotestosterone (DHT) blockers. Such solutions may be moreeffective and/or may be used in lower concentrations if they can bedelivered more effectively to the follicle area or certain portionsthereof. PDT techniques can also be used to treat hair loss asdescribed, e.g., in U.S. Pat. No. 7,090,691. Better penetration ofcompounds used in such PDT techniques into the follicle can improve theeffectiveness of such techniques.

Thus, in view of the above-described deficiencies, a method andapparatus would be desirable for improved acne treatment and treatmentof other skin conditions via more effective application of topicalsubstances into the hair follicle region and optionally into thesebaceous gland. More effective delivery of such substances can allowlower concentrations to be used, can improve efficacy, and can alsoprovide an alternative to more dangerous treatments, such as oralapplication of isotretinoin.

SUMMARY OF THE INVENTION

The present invention is directed to meeting the aforementioned needsand addressing the deficiencies particularly discussed above andgenerally in the prior art. Embodiments of the present invention providea system, method and apparatus for delivering substances, e.g.,therapeutic substances, into the hair follicle region, e.g., proximal toor into sebaceous glands, located in skin tissue. This can be achievedby directing a substance into the follicle under pressure. Optionally, aportion of the sebum present in the hair follicle may be heated and/orremoved, e.g. using a vacuum, before introducing the therapeuticsubstance.

In one aspect of the present invention, an apparatus is provided forapplying a therapeutic substance under pressure to follicle areas ofskin, e.g., to follicle openings and/or sebaceous glands. Suchapplication can improve the penetration of the substance into certainskin structures, which may improve their efficacy. The therapeuticsubstances can include, but are not limited to, topical solutions orlotions that can be used to treat acne, hair loss, follicular keratosis,or for photodynamic therapy procedures.

The apparatus can include a delivery arrangement and an outletstructured to deliver the therapeutic substance contained therein underpressure to the skin surface. The therapeutic substance can be containedwithin a reservoir or cartridge provided in the apparatus, which may bein communication with a source of pressurized gas or the like that isconfigured to propel the therapeutic substance through the outlet andinto the skin. Alternatively, the therapeutic substance can be providedto the delivery arrangement in the apparatus under pressure from aremote source.

The outlet can be configured as a single opening through the lowersurface of the apparatus that can be round, oval, a slit, or as aplurality of such openings. The openings can have a small dimension,e.g., a hole diameter or slit width, that is small to facilitateintroduction of the substance into the skin at a high pressure. Forinstance, a hole diameter or slit width can be less than about 1000 μm,e.g., less than about 500 μm, or as small as about 50 μm, or optionallyless than about 50 μm. Smaller dimensions can be used in applicationsfor which delivery of the substance into the skin at a higher pressureis desirable.

One or more vacuum conduits can be provided at least partially along alower surface of the apparatus, to improve the physical contact betweenthe lower surface and the skin during application of the therapeuticsubstance(s). One or more pressure conduits can also be provided atleast partially along a lower surface of the apparatus and configured tobe in communication with a source of pressurized gas. The pressureconduit(s) can facilitate motion of the apparatus over the skin surface,e.g., by intermittently breaking a suction force between the vacuumconduits on the lower surface of the apparatus and the skin surface.

In further embodiments of the present invention, the apparatus can alsoinclude a heating arrangement, such as a resistance heater, a source ofoptical radiation or ultrasound, or the like. The heating arrangementcan be configured to contact the skin and/or heat a portion of the lowersurface of the apparatus, to thereby heat the skin surface and loosensebum and/or other debris that may be present in pores, follicles, etc.The skin is preferably heated to a temperature less than 65° C. to avoidgenerating thermal damage to the heated tissue. The loosened materialmay then be partially removed from the skin when the one or more vacuumconduits on the lower surface pass over the heated skin. A collectionarrangement can be provided in the apparatus or affixed thereto to trapsuch material removed from the skin through the vacuum conduit(s),thereby preventing such material from being transported into thelow-pressure source and possibly contaminating or obstructing it.

In a still further embodiment, the apparatus can include a vibratingarrangement mechanically coupled or affixed to the housing. Thevibrating arrangement can be configured to induce vibrations in thehousing, including the lower surface thereof that contacts the skin whenin use. Such vibrations can facilitate movement of the apparatus overthe skin surface when a low pressure is present in the vacuum conduitand/or facilitate loosening of sebum and/or other debris that may bepresent in pores, follicles, etc.

In another aspect, embodiments of the present invention provide a methodfor introducing a therapeutic substance into a skin structure such as afollicle, pore, or sebaceous gland. The method includes optionallyheating a surface region to loosen sebum or other debris that may bepresent near the skin surface. A low-pressure arrangement can then bepassed over the heated skin tissue to loosen and/or partially removesome of the sebum and/or debris. A source of a pressurized therapeuticsubstance can then be passed over the skin surface to direct at least aportion of the substance into pores, follicles, or other skinstructures.

In yet another embodiment, the invention provides a method for treatinga subject having a skin condition. Skin conditions include acne, hairloss, follicular hyper keratosis, etc. The method comprises delivering atherapeutically effective amount of a substance under elevated pressurethrough at least one opening in a substrate onto the skin tissue of thesubject; and providing at least one low-pressure channel along a lowersurface of the substrate proximal to at least a portion of the at leastone opening, wherein the low-pressure channel is configured to maintainthe lower surface of the substrate proximal to the surface of the skintissue when a reduced pressure is provided in the low-pressure channel,thereby treating the subject for a skin condition.

In still another aspect, the invention provides kits that includevarious embodiments of the apparatus described herein and instructionsfor using the various embodiments of the apparatus in accordance withthe methods of the invention described herein.

These and other objects, features and advantages of the presentinvention will become more apparent from the following detaileddescription taken in conjunction with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

So that those having ordinary skill in the art to which the presentapplication appertains will more readily understand how to make and usethe same, reference may be had to the drawings wherein:

FIG. 1 is an illustration of a hair follicle structure;

FIG. 2a is a schematic cross-sectional illustration of an exemplaryapparatus in accordance with an embodiment of the present invention;

FIG. 2b is an illustration of the lower surface of the apparatus shownin FIG. 2 a;

FIG. 2c is an illustration of a further configuration of the lowersurface of the apparatus shown in FIG. 2 a;

FIG. 2d is an illustration of a still further configuration of the lowersurface of the apparatus shown in FIG. 2 a;

FIG. 3a is a schematic cross-sectional illustration of an exemplaryapparatus in accordance with another embodiment of the presentinvention;

FIG. 3b is an illustration of the lower surface of the apparatus shownin FIG. 3 a;

FIG. 3c is an illustration of a further configuration of the lowersurface of the apparatus shown in FIG. 3 a;

FIG. 4a is a schematic cross-sectional illustration of an exemplaryapparatus in accordance with still another embodiment of the presentinvention;

FIG. 4b is an illustration of the lower surface of the apparatus shownin FIG. 4 a;

FIG. 4c is an illustration of a further configuration of the lowersurface of the apparatus shown in FIG. 4 a;

FIG. 4d is a schematic illustration of the apparatus shown in FIG. 4abeing used to remove sebum from, and apply a therapeutic substance to, aregion of skin tissue; and

FIG. 5 is a schematic cross-sectional illustration of an exemplaryapparatus in accordance with a further embodiment of the presentinvention.

While the present invention will now be described in detail withreference to the figures, it is done so in connection with theillustrative embodiments and is not limited by the particularembodiments illustrated in the figures.

DETAILED DESCRIPTION

A schematic side view of an apparatus 200 that can be used to deliversubstances into a hair follicle and optionally to an associatedsebaceous gland is shown in FIG. 2a . The apparatus 200 includes ahousing 210, a vacuum conduit 220, and a delivery arrangement 230. Alower surface 260 of the apparatus 200 is configured to contact the skinsurface 250. In certain embodiments, the housing 210 can be shaped to beeasily held in the hand and traversed over an area of skin 250 to betreated. The delivery arrangement 230 can include a reservoir,cartridge, tube, duct, or the like, or a combination thereof, that maybe located within or formed as part of the housing 210, and that isconfigured to contain a portion of the therapeutic substance. Thetherapeutic substance in the delivery arrangement 230 can be pressurizedusing an external pressure source that can provide a pressurized gas orthe like through a delivery tube 235. The delivery arrangement 230 canalso be provided in communication with an external source or reservoirof a therapeutic substance (not shown) configured to supply thetherapeutic substance through the delivery tube 235. Vacuum conduit 220can be provided in communication with a vacuum or low-pressure source(not shown) through a vacuum tube 225. A vibrating arrangement 212 mayalso be affixed to or provided in mechanical contact with the housing210.

An exemplary configuration of the lower surface 260 of the apparatus 200is shown in FIG. 2b . The lower portion of the vacuum conduit 220 andthe lower surface 260 form a low-pressure channel 222, which can begenerally proximal to the perimeter of the lower surface 260. The outlet280 of the delivery arrangement 230 is located in the central region ofthe lower surface 260. The outside diameter of the lower surface 260 ispreferably small enough to allow the lower surface 260 to conform tolocal variations in the shape of the skin surface 250, and large enoughto facilitate treatment of larger areas of the skin 250. For example,the outside diameter of the lower surface 260 can be between about 1inch and about 3 inches, although smaller or larger diameters can beprovided in certain embodiments. The shape of the lower surface 260 canbe substantially circular, as shown in FIG. 2b . In further embodiments,the lower surface 260 can be ovoid, elliptical, or polygonal in shape,or any other shape appropriate for a particular application. The lowersurface 260 can be substantially flat, or it may be slightly convex,concave, or otherwise contoured to more closely adapt to the shape of askin surface 250 to be treated.

In use, the apparatus 200 can be placed against the skin 250 and a lowpressure or vacuum provided in the vacuum conduit 220. The low pressureor vacuum can be controlled, e.g., using a conventional valvearrangement or the like. The low pressure in the vacuum conduit 220 andlow-pressure channel 222 can facilitate close contact and/or adherencebetween the lower surface 260 of the apparatus 200 and the skin surface250. A therapeutic substance can be provided under elevated pressure inthe delivery arrangement 230, e.g., using the delivery tube 235. Thetherapeutic substance can be provided in the form of an aqueoussolution, another type of liquid solution, a lotion, a suspension oremulsion, or the like. The therapeutic substance can then be deliveredinto hair follicle regions in the skin 250 located proximal to theoutlet 280 of the delivery arrangement 230. The elevated pressureprovided in the delivery arrangement 230 can facilitate such delivery.In certain embodiments, one or more low-pressure channels 222 and/orvacuum conduits 220 can be used to recover a portion of the therapeuticsubstance from the skin surface that is delivered by the deliveryarrangement 230 but not absorbed into the skin openings. Such recoverycan be used, e.g., to eliminate a presence of excess therapeuticsubstance on the skin surface after treatment and/or to recoverexpensive therapeutic substances or components thereof, such as goldnanoparticles or the like.

In certain embodiments, the pressure in the delivery arrangement 230 canbe varied over time, e.g., to provide a pulsed delivery of thetherapeutic substance. For example, the delivery arrangement 230 can beexposed to intervals of high pressure that may have a regular period orfrequency, or which may be randomly timed. The pressure variations orpulses can facilitate introduction of the therapeutic substance into theopenings of the skin tissue, such as the follicles and pores. Theintervals can be of short duration, e.g., on the order of a second orless. In certain embodiments, longer intervals of high pressure may beused. Such variations in pressure applied to the therapeutic substanceduring delivery may be used with any of the various embodiments of thepresent invention described herein.

The low pressure provided in the vacuum conduit 220 and low-pressurechannel 222 can also help prevent a portion of the therapeutic substancefrom escaping out the sides of the lower surface 260 of the apparatus200 when it is delivered under pressure, while preferably not removing asignificant amount of the therapeutic substance that was introduced intothe skin through the outlet 280. The size, shape and/or geometry of thelow-pressure channel 222 can be selected to optimize these differentfunctions when the device is passed over the skin at reasonable/typicaloperating speeds. For example, a portion of the therapeutic substancethat is forced through the outlet 280 but does not penetrate or absorbinto the follicle areas of the skin 250 may be recovered through thelow-pressure channel 222 and vacuum conduit 220.

The apparatus can be traversed over the skin surface 250 to treat alarger area of skin. The presence of low pressure in the vacuum conduitcan impede mobility of the apparatus 200 over the skin surface 250.However, it has been observed that providing a pressurized source suchas that present at the outlet 280 of the delivery arrangement 230provides an intermittent breaking and recovery of the vacuum sealbetween the low-pressure channel 222 at the lower surface 260 of theapparatus 200 and the skin surface. Such behavior can manifest as avibration of the apparatus 200, and facilitates easy motion of theapparatus 200 over the skin surface 250.

In a further embodiment, the apparatus 200 can include a pressureconduit 270 configured to be proximal to at least a portion of thevacuum conduit 220 on the lower surface 260 of the apparatus 200, asshown in FIG. 2c . The pressure conduit 270 can have a form generallysimilar to that of the low-pressure channel 222 shown in FIG. 2a . Asource of pressurized gas, such as air, nitrogen, or the like, can beprovided to the pressure conduit 270 using a hose, tubing or the like.The pressure in the pressure conduit 270 can be controlled using aconventional valve arrangement. In use, the low-pressure channel 222 canprovide good adherence between the apparatus 200 and skin surface 250,as described above. The pressure in the pressure conduit 270 can becontrolled and/or adjusted to modify this adherence and allow theapparatus 200 to be easily traversed over the skin 250, substantiallyindependent of the pressurized therapeutic substance provided throughthe outlet 280 of the delivery arrangement 230.

In certain embodiments, the relative locations of the low-pressurechannel 222 and pressure conduit 270 can be reversed from that shown inFIG. 2c , such that the pressure conduit 270 lies outside of thelow-pressure channel 222, e.g., closer to the outer edge of the lowersurface 260 of the apparatus 200. In still further embodiments, thelow-pressure channel 222 and/or the pressure conduit 270, if present,can be provided as a plurality of openings on the lower surface 260 ofthe apparatus 200, e.g., as a plurality of rectangular or curved slots,rather than as continuous channels such as those shown in FIGS. 2b and 2c.

Pressure provided to the pressure conduit 270 (if present) and/or thedelivery arrangement 230, and vacuum in the vacuum conduit 220 andlow-pressure channel 222 can be controlled individually to provide goodadherence of the apparatus 200 to the skin 250 and desired delivery ofthe therapeutic substance to the skin 250, while also facilitatingmotion of the apparatus 200 over the skin surface 250. For example, theamount of pressure or vacuum applied to these conduits can be set orvaried using conventional valve arrangements and/or pressurecontrollers. The pressures and/or vacuum may optionally be pulsed tofacilitate such motion.

The outlet 280 of the delivery arrangement 230 can be provided as asingle opening, similar to that shown in FIG. 2b . Alternatively, theoutlet 280 can be configured as a plurality of smaller openings ornozzles, as shown in FIG. 2d . The smaller openings of the outlet 280can be used to deliver the therapeutic substance at higher localpressures, which can facilitate infiltration of such substance into thefollicle region and optionally into sebaceous glands. For example, theoutflow pores may have a lateral size or diameter that is between about50 μm and about 500 μm. Accordingly, the streams of the therapeuticsubstance that may be provided through the optional openings or nozzlescan have a size that is less than about 1000 μm, e.g., less than about500 μm, or as small as about 50 μm, or optionally less than about 50 μm.The delivery stream or streams can be used to force solutions orsubstances into the at least partially open sebaceous follicles.

The vibrating arrangement 212 may optionally be provided in theapparatus 200. The vibrating arrangement 212 can be mechanically coupledto the housing 210, and configured to generate vibrations in thehousing, e.g., on the lower surface 260, when the device 200 is in use.The vibrating arrangement 212 can include, e.g., an eccentric weightprovided on a rotating shaft, a piezoelectric element, or anyconventional device configured to produce vibrations. Vibrationsgenerated by the vibration arrangement 212 can facilitate translation ofthe apparatus 200 over the skin tissue 250 when in use. They can alsoassist in breaking up, loosening, and/or removing sebum and/or otherdebris that may be present near the surface of the skin 250. Suchremoval of sebum and/or debris is described in more detail below.

The vibrating arrangement 212 can have an amplitude of vibration in therange of about 50-1000 or between about 100-500 μm. The frequency of theinduced vibrations can be between about 1 Hz and about 10 kHz. Othervibration parameters may be used in certain embodiments. Particularvibration parameters can be selected based on properties of theapparatus 200, e.g., the size of the apparatus 200 and/or the lowersurface 260, the size and shape of the vacuum conduit 220 and/or thedelivery arrangement 230, the pressures provided in these structures,etc. The vibrating arrangement 212 can include circuitry configured toadjust the amplitude and/or frequency of the vibrations. The vibrationarrangement 212 can optionally be included with other embodiments of thepresent invention described herein.

In a further embodiment, an apparatus 300 shown in FIG. 3a can beprovided for delivering substances into a hair follicle and optionallyto an associated sebaceous gland. The apparatus 300, similar to theapparatus 200 shown in FIG. 2a , includes a housing 310, a vacuumconduit 320, and a delivery arrangement 330. A handle 340 can beattached to the housing 310 or formed as part of the housing 310 tofacilitate manipulation of the apparatus 300. The delivery arrangement330 can be provided in communication with a source or reservoir of atherapeutic substance (not shown) through a delivery tube 335, and thevacuum conduit 320 and low-pressure channel 322 can be provided incommunication with a vacuum or low-pressure source (not shown) through avacuum tube 325.

An exemplary configuration of the lower surface 360 of the apparatus 300is shown in FIG. 3b . The lower surface 360 can have a substantiallysquare or rectangular shape, as shown in FIG. 3b , and other shapes mayalso be used. The lower portion of the vacuum conduit 320 and the lowersurface 360 form the low-pressure channel 322, which may be generallyproximal to the perimeter of the lower surface 360. The outlet 380 ofthe delivery arrangement 330 can be configured as an elongated slitextending through the lower surface 360. Such a slit can provide a highdelivery pressure for the therapeutic substance delivered through thedelivery arrangement 330, and the delivery can easily be applied over alarge area of skin when the lower surface 360 of the device 300 istraversed over a skin surface in the direction of the arrow shown inFIG. 3 b.

In a further embodiment, shown in FIG. 3c , the outlet 380 of thedelivery arrangement 330 can be configured as a plurality of elongatedslits extending through the lower surface 360. The slits can be arrangedin one or more rows, as shown in FIG. 3c , or other configurations mayalso be used. Such slits can also provide a high delivery pressure forthe therapeutic substance delivered through the delivery arrangement330.

In another embodiment, the apparatus 300 can include a pressure conduitsimilar to the pressure conduit 270 shown in FIG. 2c . This pressureconduit can be provided proximal to the low-pressure channel 322 on thelower surface 360 of the apparatus 300, and a gas pressure in thepressure conduit can be controlled and/or adjusted to facilitatetraversal of the apparatus 300 over the skin surface, substantiallyindependent of the pressurized therapeutic substance provided throughthe outlet 380.

A further embodiment of an apparatus 400 that can be used to deliversubstances into a hair follicle and optionally an associated sebaceousgland is shown schematically in FIG. 4a . The apparatus 400 includes ahousing 410, a vacuum conduit 420, and a delivery arrangement 430. Alower surface 460 of the apparatus 400 can be, e.g., affixed to thehousing 410 or formed as an integral part thereof. An outlet 480 can beprovided that allows material located in the delivery arrangement 430 topass through the lower surface 460. The lower portion of the vacuumconduit 420 and the lower surface 460 form a low-pressure channel 422.The housing 410 can include a handle 440 that facilitates manipulationof the apparatus 400, e.g., to translate it over an area of skin to betreated. The delivery arrangement 430 can be provided in communicationwith a source or reservoir of a therapeutic substance (not shown)through a delivery tube 435.

The vacuum conduit 420 and low-pressure channel 422 can be provided incommunication with a vacuum pump or low-pressure source (not shown)through a vacuum tube 425. The pressure within the low-pressure channel422 is preferably low enough to substantially maintain good contactbetween the skin and the lower surface 460 of the apparatus 400 when inuse. Any pressure that is lower than atmospheric pressure may beprovided in the vacuum conduit 420. The pressure is preferably greaterthan about 11 psi (e.g., greater than about −0.8 atmospheres). Exposureof the skin tissue to pressures lower than this may generate somepetechial hemorrhage and/or bruising of the skin. However, applicationof a pressurized environment (e.g., a pressure greater than atmosphericpressure) proximal to the region of tissue exposed to such lowerpressure can reduce the likelihood of bruising or hemorrhage. Suchhigher pressure can be provided, e.g., by the pressurized substancebeing delivered from the delivery arrangement 430 through the conduit480 and/or by a pressurized outlet provided in proximity to thelow-pressure channel 422, e.g., similar to the pressurized conduit 270shown in FIG. 2 c.

The apparatus 400 further includes a heating arrangement 490. Theheating arrangement 490 can include a conventional resistance heater orother heating device, and preferably includes an on/off switch and acontroller, e.g., a thermostatic controller or the like. The heatingarrangement 490 can provide contact or radiant energy heating of theskin tissue near the surface. For example, the heating arrangement 490may include electrical resistance heating, infrared or other opticalheating (e.g., using a plurality of LEDs, laser diodes, lamps),ultrasound, or other sources configured to emit energy at one or morewavelengths absorbed by the skin and/or the sebum, phase-change orchemical reaction heating (e.g., providing one or more warm orexothermically reactive substances in a chamber within the device), etc.

The size, duration, temperature (for conductive contact heating) orexposure parameters of irradiance, wavelength(s) and exposure time forradiant heating of the heating arrangement 490 are preferably selectedsuch that the sebum and debris are sufficiently heated to loosen themand/or facilitate their removal when the apparatus 400 is moved over theskin at reasonable/typical operating speeds. Such speeds can be, e.g.,on the order of about 1 cm/sec, although higher or lower speeds can alsobe used. The heating arrangement 490 can facilitate introduction of thetherapeutic substance into the follicle region and optionally intosebaceous glands by heating and loosening accumulated sebum in thefollicle region. A portion of this sebum may also be removed using theapparatus 400, as described in more detail below.

An exemplary configuration of the lower surface 460 of the apparatus 400is shown in FIG. 4b . The outlet 480 of the delivery arrangement 430 islocated in the central region of the lower surface 460. The lowerportion of the vacuum conduit 420 and the lower surface 460 form thelow-pressure channel 422 in the lower surface 460 that may be generallyproximal to the perimeter of the lower surface 460. A portion 422 a ofthe low-pressure channel 422 proximal to the heating arrangement 490 maybe wider than other parts of the low-pressure channel 422 to facilitateremoval of sebum in the skin, as described in more detail below. Incertain embodiments, two or more low-pressure channels 422 may beprovided. Thus, for example, the wider portion 422 a of the low-pressurechannel 422 shown in FIG. 4b can optionally be provided as a secondchannel that is separate from the narrower portion of the low-pressurechannel 422.

A surface of the heating arrangement 490 is preferably configured to besubstantially coplanar with the lower surface 460, such that it willcontact the skin surface when the lower surface 460 of the device 400 isplaced on the skin. In another embodiment, the heating arrangement 490can be located above a portion of the lower surface 460, e.g., withinthe housing 410, and configured to heat a portion of the lower surface460 and a region of skin contacting the heated portion of the lowersurface 460.

In a further embodiment, the apparatus 400 can include a pressureconduit 470 proximal to at least a portion of the low-pressure channel422 on the lower surface 460 of the apparatus 400, as shown in FIG. 4c .The pressure conduit 470 can be similar to the pressure conduit 270shown in FIG. 2c , and may be provided to facilitate translation of theapparatus 400 over a skin surface when a vacuum or low pressure ispresent in the low-pressure channel 422 and/or to reduce or preventbruising of skin that is exposed to the low pressure. A source ofpressurized gas, such as air, nitrogen, or the like, can be provided tothe pressure conduit 470 using a hose, tubing or the like, and the gaspressure can be controlled using a conventional valve arrangement.Pressure provided to the pressure conduit 470 may optionally be pulsedto facilitate translation of the apparatus 400.

The geometry of the pressure conduit 470 and its location relative tothe vacuum conduit 420 may be varied from the configuration shown inFIG. 4c . In general, portions of the pressure conduit 470 that passthrough the lower surface 460 of the apparatus 400 are preferablylocated proximal to portions of the low-pressure channel 422. Forexample, the pressure conduit 470 may be configured as a plurality ofchannels provided substantially parallel to portions of the low-pressurechannel 422 on the lower surface 460. Such proximity can facilitateintermittent interruption of a vacuum seal that may be formed betweenthe low-pressure channel 422 and the skin surface as described above,and allow the apparatus 400 to more easily be translated over the skinwhen a low pressure is present in the vacuum conduit 420.

FIG. 4d illustrates an exemplary use of the apparatus 400 to deliver atherapeutic material 433 into one or more sebaceous glands 495 locatedin the skin 450. The apparatus 400 is placed on the surface of the skin450. The low-pressure channel 422 facilitates good contact between thelower surface 460 of the apparatus 400 and the skin 450 when a lowpressure is provided in the vacuum conduit 420. The apparatus 400 can betranslated over the surface of the skin 450 in the direction indicatedby the arrow in FIG. 4 d.

The heating arrangement 490 provided in a forward location of theapparatus will first contact a target area of the skin 450, and can becontrolled to heat sebum 492 and any associated debris located in thetarget area. Such heating can loosen the sebum 492, e.g., by melting orreducing the viscosity of wax esters of the sebum 492 that may bepresent in or proximal to sebaceous glands 495 that block access to thefollicle opening and sebaceous gland 495.

For example, the target area of the skin 450 can be heated to atemperature of between about 37° C. and about 47° C. Heating of the skintissue 450 to higher temperatures can also be performed. Heatingtemperatures may preferably be greater than about 35° C., which may beslightly lower than the body's core temperature but greater than atypical surface temperature of the skin 450. Preferably, the target areaof the skin 450 is heated to a temperature that is less than about 65°C., to avoid the likelihood of generating irreversible thermal damage insurrounding dermis tissues. Sebaceous glands 495 are generally locatedabout 1-2 mm deep below the surface of the skin 450. Heat transfer byconduction through the skin 450 to the level of the sebaceous gland 495may require several seconds or more, depending on depth of the featuresbeing heated.

Preheating of skin tissue 450 to be treated can optionally be performedprior to using an apparatus in accordance with certain embodiments ofthe present invention described herein. For example, radiant heating orcontact heating using, e.g., a heated pad, a hot towel, or the like canbe performed on the skin 450 prior to application of an apparatus 200,300, 400 to the heated skin 450. In certain embodiments, such preheatingcan be performed instead of providing a heating arrangement 490 in theexemplary apparatus 400. Alternatively, such preheating can be performedin addition to using such a heating arrangement 490.

As the apparatus 400 is traversed over the skin 450, a forward portion422 a of the low-pressure channel 422 (which may optionally be widerthan other parts of the low-pressure channel 422) passes over the heatedtissue, and the low pressure can facilitate loosening and/or removal ofa portion of the heated sebum 492 and/or debris from sebaceous glands495, follicles, and/or pores in the skin 450. The vacuum procedure canalso remove some blockages that may be present in the duct of thesebaceous gland 495 and/or in follicles, which may be achieved withother embodiments of the present invention described herein that do notinclude a heating arrangement 490.

Removal of sebum 492 and/or other debris in the follicle region can beenhanced, e.g., by applying a force in the vicinity of a hair folliclethat has a lateral component (e.g., parallel to the skin surface), suchthat material in the infidibulum can be squeezed out. Such force may beapplied by edges of the lower surface 460 of the apparatus 400 as it istranslated over the skin 450. The low pressure in the low-pressurechannel 422 can pull the skin 450 against the lower surface 460 of theapparatus 400 as it is translated, thus increasing the effectiveness ofsuch removal.

The outlet 480 of the delivery arrangement 430 can be located behind thewide portion 422 a of the low-pressure channel 422 (relative to thepreferred translation direction of the apparatus 400 indicated by thearrow in FIG. 4d ), as shown in FIG. 4b . The width of the outlet 480 ispreferably similar to that of the wide portion 422 a of the low-pressurechannel 422, e.g., it may be slightly narrower as shown in FIG. 4b . Asthe apparatus 400 continues to be traversed over the skin 450, atherapeutic substance 433 provided under pressure in the deliveryarrangement 430 can be forced through the conduit 480 and into thefollicle region of the target area, e.g., into the sebaceous glands 495from which some sebum 492 and debris may have previously been loosenedand/or removed. Removal of sebum 492 can generate a more open pathwaythat facilitates penetration of such therapeutic substance 433 moredeeply into the follicle and/or sebaceous gland 495.

The therapeutic substance 433 is preferably provided in the deliveryarrangement 430 under pressure. In certain embodiments, multipledelivery arrangements 430 and/or outlets 480 can be provided that areconfigured to deliver two or more different types of therapeuticsubstances 433. The delivery arrangement 430 may include a reservoir,cartridge, or the like that may be located within the housing 410 orformed as part of the housing 410 that is configured to contain thetherapeutic substance 433. The therapeutic substance 433 can bepressurized using, e.g., a pressure source such as a manual or electricpump, a piston, a pressurized gas line provided in communication withthe delivery arrangement 433, or the like.

In certain embodiments, the outlet 480 can be provided in the form ofone or more smaller nozzles, orifices, jets, or slits through the lowersurface 460 that are configured to direct one or more small streams ofthe therapeutic substance 433 onto the skin surface 450 and into thefollicle region and/or sebaceous glands 495. Such nozzles or jets can beprovided in a substantially linear array (e.g., in a single row) toexpose a large portion of the skin surface to the streams when theapparatus is traversed over the skin surface. Alternatively, the jets ornozzles can be arranged in a two-dimensional array (e.g., two or morerows of nozzles, jets, slits, etc.) to provide greater exposure of theskin surface 450 to the plurality of streams of pressurized therapeuticsubstance 433 as the apparatus 400 is translated over the skin surface450.

In further exemplary embodiments, the apparatus 400 can include aplurality of low-pressure channels 422 and/or delivery arrangements 430and outlets 480, which may be configured such that a particular follicleor pore is exposed to more than one cycle of low-pressure removal anddelivery of pressurized substance(s) as the apparatus 400 is translatedover the follicle or pore. Multiple heating arrangements 490 can also beprovided. Such exemplary configurations can improve the effectivenessfor skin heating, removal of sebum, and/or delivery of therapeuticmaterial(s). Alternatively, the apparatus 400 (or any apparatus inaccordance with embodiments of the present invention) may be translatedover a region of skin to be treated a plurality of times to generatemultiple cycles of heating, sebum removal, and/or delivery oftherapeutic substances.

A further embodiment of an apparatus 500 in accordance with the presentinvention is shown in FIG. 5. The apparatus 500 includes a housing 510,a vacuum conduit 520, a low-pressure channel 522 (optionally including awide portion 522 a), a delivery arrangement 530, and a heatingarrangement 590. The housing 510 can include a handle 540 thatfacilitates manipulation of the apparatus 500. A lower surface 560 ofthe apparatus 500 can be affixed to the housing 510 or formed as anintegral part thereof.

The delivery arrangement 530 can include a reservoir, cartridge,enclosure or the like adapted to hold a therapeutic substance 533. Thedelivery arrangement 530 can be provided in communication with apressure source through delivery tube 535, such that the therapeuticsubstance 533 can be delivered under pressure from an outlet 580 locatedon the lower surface 560 of the apparatus 500 and into the skin. Acontrol conduit 538 may also be provided in communication with thedelivery arrangement 530, e.g., as shown in FIG. 5. A distal end of thecontrol conduit 538 can pass through the lower surface 560 of theapparatus 500 at one or more locations thereon.

The control conduit 538 can act as a control valve for pressurizing thetherapeutic substance 533 in the delivery arrangement 530. For example,when the lower surface 560 of the apparatus 500 is placed in contactwith a skin surface, the distal end of the control conduit 538 can beblocked, allowing a pressurized gas provided through the delivery tube535 to force some of the therapeutic substance 533 through the outlet580. When the lower surface 560 of the apparatus 500 is not in contactwith a skin surface, the pressurized gas will more readily flow throughthe control conduit 538 and out of the unobstructed distal end thereof,thereby preventing the therapeutic substance 533 from being pushed outof the outlet 580 when it is not proximal to a skin surface. A manualswitch or valve may also be provided, in addition to or instead of thecontrol conduit 538, to control the delivery of pressurized therapeuticsubstance 533 through the outlet 580 and into a region of skin to betreated. The control conduit 538 can also be provided with otherembodiments of the present invention described herein to controlapplication of the therapeutic substance 533.

A collection arrangement 528 may also be provided in communication witha vacuum tube 525 and the vacuum conduit 520. The collection arrangement528 can be configured to trap sebum or other material that may bewithdrawn from the skin being treated through the vacuum conduit 520,while preventing the sebum from passing through the vacuum tube 525 thatprovides low pressure to the vacuum conduit 520 and low-pressure channel522. The collection arrangement 528 can be provided within the housing510 of the apparatus 500 as shown in FIG. 5, or external to the housing510. The collection arrangement 538 may also be provided with otherembodiments of the present invention described herein.

An apparatus for delivering a substance to hair follicles, pores and/orsebaceous glands in the skin, in accordance with the various embodimentsof the present invention described herein, can be provided as adisposable device. For example, such an apparatus can be provided as ahousing that includes one or more vacuum conduits and deliveryarrangements with associated outlets, as described herein. The apparatuscan be configured to be attached to a low-pressure or vacuum source anda pressure source through a vacuum tube and a delivery tube,respectively. The housing can be configured to accept one or morecartridges, vials, or the like containing one or more therapeuticmaterials. The housing can also be configured to accept a removable andreusable heating arrangement affixed thereto. A collection arrangementcan also be included in the housing.

In use, a cartridge containing a therapeutic substance can be affixed tothe device such that the substance is in communication with the deliveryarrangement. A high-pressure source and a low-pressure source can alsobe attached to the device. An optional heating arrangement can also beaffixed to the device. The device can then be applied to a skin surfaceas described herein, to apply the therapeutic substance into poresand/or follicle regions of the skin, and optionally to loosen and/orremove a portion of the sebum present. After use, the cartridge andheating arrangement can be removed from the device, and the devicedisconnected from the low- and high-pressure sources. The device canthen be discarded, while the heating arrangement and/or cartridge can beused with a new device for a further treatment.

Any therapeutic substance that can produce a desirable effect whendelivered into a hair follicle and/or into a sebaceous gland (e.g., notjust limited to acne treatments) may be used in embodiments of thepresent invention. Such therapeutic substances can penetrate moreeffectively into the follicle and/or sebaceous gland, as compared with aconventional topical application, using the exemplary method andapparatus described herein.

For example, one therapeutic substance that may be used is a topicalretinoid (e.g., tretinoin) for treatment of acne conditions. ALA orother compounds used in PDT for acne treatment, hair loss treatment, orthe like, such as those described in U.S. Pat. Nos. 6,897,238,6,034,267, and 7,090,691, may also be used. Topical solutions of vitaminA or benzoyl peroxide may be used to treat follicular keratosis. Othertherapeutic substances that are marketed as topical solutions forvarious uses such as treating hair loss or various dermatologicalconditions may also be used with embodiments of the present invention.For example, solutions for treating hair loss that contain substancessuch as minoxidil, azealic acid, and/or dyhydrotestosterone (DHT)blockers may be used. Therapeutic substances containing antimicrobialmetal nanoparticles, such as those described in U.S. Pat. No. 7,008,647or the like, may also be used. Therapeutic substances containingchromophores, e.g. exogenous chromophores, such as those described inU.S. Pat. No. 7,494,503 for use in PDT procedures can also be used withembodiments of the present invention. Such substances and/or proceduresusing such substances may be more effective if they can be deliveredmore effectively to the follicle area or certain portions thereof.

Various therapeutic substances, including any mentioned herein orcombinations thereof, can also be applied using embodiments of thepresent invention. Accordingly, amounts and/or concentrations of suchapplied therapeutic substances may be reduced and still provide similareffectiveness. This approach may also improve the efficacy of topicalsolutions and/or reduce the occurrence of undesirable side effects,because the therapeutic substances can be delivered more specificallyinto the regions of the follicle to be treated. In some applications,using sufficient degrees of preheating, vacuum, and pressurized deliverymay allow some amount of the therapeutic substances to be delivered intothe sebaceous gland.

The foregoing merely illustrates the principles of the invention.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous techniques which, although not explicitly describedherein, embody the principles of the invention and are thus within thespirit and scope of the invention. All patents and publications citedherein are incorporated herein by reference in their entireties.

What is claimed is:
 1. A system of treating a sebaceous gland in humanskin with light energy to reduce acne symptoms, the system comprising: acomposition comprising a metallic nanoparticle dispersed within acarrier; means to vibrate at least a portion of the skin surface towhich the composition is applied; means to selectively remove at leastsome of the composition from the skin surface after application of themeans to vibrate, while leaving the metallic nanoparticles in proximityto or within the sebaceous gland; and means to optically irradiate theskin to which the composition was applied with light energy afterremoval of at least some of the composition from the skin surface.